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Modelling genetic reorganization in the mouse spinal cord affecting left-right coordination during locomotion
Journal article   Open access   Peer reviewed

Modelling genetic reorganization in the mouse spinal cord affecting left-right coordination during locomotion

Ilya A Rybak, Natalia A Shevtsova and Ole Kiehn
The Journal of physiology, v 591(22), pp 5491-5508
15 Nov 2013
DOI: https://doi.org/10.1113/jphysiol.2013.261115
PMID: 24081162
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1113/jphysiol.2013.261115View
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Abstract

Interneurons - physiology Motor Activity - physiology Tumor Suppressor Proteins - metabolism Locomotion - genetics Spinal Cord - metabolism Netrin-1 Axons - metabolism Receptor, EphA4 - metabolism Axons - physiology Nerve Growth Factors - metabolism Gait - physiology Nerve Net - physiology Mice, Knockout Motor Activity - genetics Animals Interneurons - metabolism Nerve Growth Factors - genetics Receptor, EphA4 - genetics Spinal Cord - physiology Tumor Suppressor Proteins - genetics Nerve Net - metabolism Mice Models, Neurological Locomotion - physiology
The spinal neural circuit contains inhibitory (CINi) and excitatory (CINe) commissural interneurons with axons crossing the mid-line. Direction of these axons to the other side of the cord is controlled by axon guidance molecules, such as Netrin-1 and DCC. The cord also contains glutamatergic interneurons, whose axon guidance involves the EphA4 receptor. In EphA4 knockout (KO) and Netrin-1 KO mice, the normal left-right alternating pattern is replaced with a synchronized hopping gait, and the cord of DCC KO mice exhibits uncoordinated left and right oscillations. To investigate the effects of these genetic transformations, we used a computational model of the spinal circuits containing left and right rhythm-generating neuron populations (RGs), each with a subpopulation of EphA4-positive neurons, and CINi and CINe populations mediating mutual inhibition and excitation between the left and right RGs. In the EphA4 KO circuits, half of the EphA4-positive axons crossed the mid-line and excited the contralateral RG neurons. In the Netrin-1 KO model, the number of contralateral CINi projections was significantly reduced, while in the DCC KO model, the numbers of both CINi and CINe connections were reduced. In our simulations, the EphA4 and Netrin-1 KO circuits switched from the left-right alternating pattern to a synchronized hopping pattern, and the DCC KO network exhibited uncoordinated left-right activity. The amplification of inhibitory interactions re-established an alternating pattern in the EphA4 and DCC KO circuits, but not in the Netrin-1 KO network. The model reproduces the genetic transformations and provides insights into the organization of the spinal locomotor network.

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21 citations in Web of Science
22 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Neurosciences
Physiology
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